Cetuximab is a chimeric IgG1 monoclonal antibody against epidermal growth factor receptor. It is approved by the European medical agency for the treatment of RAS wild-type metastatic colorectal cancer and metastatic squamous cell cancer of the head and neck. Few cases of aseptic meningitis, primarily associated with the first administration of cetuximab in patients with squamous cell cancer, have been reported. So far, there was only 1 case in a patient with metastatic colorectal cancer. We report on a 50-year-old Caucasian patient with metastatic rectum carcinoma who suffered from headache, fever, and neck stiffness 3 h after the first administration of cetuximab (400 mg/m). CSF examination revealed an excessive pleocytosis with a white blood cell count of 2,433/µL. He was diagnosed with cetuximab-induced aseptic meningitis since clinical symptoms and CSF pleocytosis resolved within days, and further diagnostic workup revealed no infectious cause. Cetuximab-induced aseptic meningitis is a rare and severe drug reaction with predominance in treating squamous cell cancer of the head and neck. Clinical presentation and CSF findings suggest acute meningoencephalitis. In all reported cases, the course of the disease was benign and self-limited. Empiric antimicrobial and antiviral therapy are suggested until infectious causes can be ruled out. A lower dosage of cetuximab and a premedication including antihistamines and glucocorticosteroids may lower the risk of a re-occurrence if cetuximab therapy is continued.